Cells are cultured by seeding them into a culture dish, where the cells experience a recovery phase after being removed from their primary environment. Eventually, the cells settle and undergo exponential growth until they approach confluency, at which point contact inhibition occurs and the cells enter a plateau stage of growth. In order for cells to grow beyond confluency they generally must be passaged (separated). Passaging may be performed, for example, by dividing the cells into multiple culture containers at a known concentration and adding fresh media to the containers.
Human embryonic stem cells are examples of cultured cells that are valuable both for research and therapeutic purposes. These cells, harvested from the inner cell mass of an early embryo, can proliferate indefinitely while retaining the ability to give rise to any part of the body. However, cell cultivation generally requires that the cultured stem cells be passaged into separate portions using mechanical, enzymatic or chemical methods. The separated portions of the cell colony are then used to seed cultures and establish new colonies of stem cells, often in viscous or gel-like media. There are advantages and disadvantages to using either mechanical dissection or chemical/enzymatic methods.
Some studies indicate that manual passaging better preserves the karyotype of the stem cells. Conventional techniques for manually dissecting a cell colony involve cutting the cell colony with the edge of a sharp object, such as the broken tip of a glass pipette. A commercial version of this device, the Stem Cell Cutting Tool, is available from Swemed Lab International AB of Billdal, Sweden. However, manual dissection can be time consuming because bulk passaging is typically not possible using physical dissection. Numerous individual cuts are therefore typically needed to dissect a cell colony. In addition, physical dissection can result in cell colony portions having non-homogenous sizes or shapes. In contrast, while enzymatic digestion allows for bulk passaging, it is typically more likely to induce chromosomal changes in the cells.
U.S. Published Application 2004/0138686 (the '686 Publication) purports to describe a tool that can be used to cut a cell colony into multiple pieces with one pass of the tool. Specifically, this publication describes a tool having a handle and an incision knife module having multiple fixed or rolling blades. However, this tool may suffer from a number of disadvantages. For example, the tool may not only cut the cell colony, but an underlying surface, such as a plate. If the underlying surface is cut, it can be difficult to dislodge and harvest the cut cell colony pieces. Also, when cutting the cell colony, parts of the colony may be pushed into the spaces between the knife blades. If this occurs, the tool may have reduced cutting efficiency and may damage the cell colony, as well as cells crushed in the spaces between the knife blades. Accumulation of material between the blades may require more frequent cleaning or make the tool more difficult to clean.
The tools disclosed in the '686 Publication appear to have relatively narrow cutting widths, such as 1 cm or less. If the substrate to be cut is relatively large, a greater number of cutting passes are likely to be required, increasing the time needed to dissect the colony, potentially decreasing cut homogeneity, and possibly leading to increased fouling of device. Additionally, the small size of the device may make it difficult to construct, assemble, or disassemble.